Regulation of Reproductive Activity by Steroid Hormone Metabolizing Enzymes

类固醇激素代谢酶对生殖活动的调节

• 批准号: 63480089
• 负责人: TAKAHASHI Michio
• 金额: $ 4.29万
• 依托单位: Faculty of Agriculture, The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480089/
• 关键词: Pregnancy; Corpus luteum; Progesterone; 20alpha-hydroxysteroid dehydrogenase; Prolactin; steroid hormone metabolizing enzyme; Ovary; 20alpha-dihydroprogesterone; 20αーダイハイドロプロゲステロン; 20d-hydroxysteroid dehydrogenase(20d-HSD); progesterone; 20d-di

20a-hydroxysteroid dehydrogenase (20alpha-HSD) catabolizes progesterone, which plays a crucial role to achieve and maintain pregnancy and is a major precursor of several steroid hormones, into biologically inactive 20a-dihydroprogesterone and plays important roles in steroid metabolism. Especially in rodents, the increase of this enzyme activity in the corpus luteum causes the rapid decrease of peripheral progesterone levels and this mechanism enable rodents to actualize very short ovulation cycle (about 4 days per a cycle). Pregnancy of the rodents is achieved and maintained by the inhibition of this increase in 20alpha-HSD activity by prolactin (PRL). In this research, we studied about this enzyme and the mechanism of the regulation of the activity at cellular and molecular level, and the results are as follows.1) Ovarian 20alpha-HSDs were completely purified 2) There are two types of 20alpha-HSD with very close molecular weight (33,000) and with different ionic strengths.3) Anti-20alpha-HSD antiserum were obtained, and cellular and intracellular localization was analyzed by immunocytochemi story and western blotting.4) We found that suppressive action of PRL on the enzyme activity is mediated by transforming growth factor-beta (TGF-beta) which is produced by luteal macrophages.5) cDNA library of rat ovary was prepared to get clone of 20alpha-HSD cDNA.

20a-羟基类固醇脱氢酶（20α - hsd）将孕酮分解为无生物活性的20a-二氢孕酮，在类固醇代谢中发挥重要作用。孕酮是实现和维持妊娠的关键物质，是几种类固醇激素的主要前体。特别是在啮齿类动物中，黄体中该酶活性的增加导致外周孕酮水平的迅速下降，这一机制使啮齿类动物的排卵周期非常短（每周期约4天）。通过泌乳素（PRL）抑制20 α - hsd活性的增加，实现并维持了啮齿动物的妊娠。在本研究中，我们从细胞和分子水平对该酶及其活性调控机制进行了研究，结果如下：1)卵巢20 α - hsd完全纯化2)20 α - hsd有两种分子量非常接近（33000），离子强度不同的类型。3)获得抗20 α - hsd抗血清，通过免疫细胞化学和western blotting分析细胞和细胞内定位。4)我们发现PRL对酶活性的抑制作用是通过黄体巨噬细胞产生的转化生长因子- β (tgf - β)介导的。5)建立大鼠卵巢cDNA文库，获得20 α - hsd cDNA克隆。

项目成果

Kadota, T., M. Ohta, M. Takahashi: "Dynamic response to follicle-stimulating hormone of secretion of progesterone by superfused rat ovarian granulosa cells." Mol. Cell. Endocrinol., 59, 213-220, 1988.

Kadota, T.、M. Ohta、M. Takahashi：“灌注的大鼠卵巢颗粒细胞分泌黄体酮对促卵泡激素的动态反应。”

Noda,K.,K.Shiota,M.Takahashi: "Purification and characterization of rat ovarian 20α-hydroxysteroid dehydrogenase." Biochemical Journal. (1990)

Noda, K.、K. Shiota、M. Takahashi：“大鼠卵巢 20α-羟基类固醇脱氢酶的纯化和表征”（生化杂志）。

Saito,S.,S.Matsuyama,K.Shiota and M.Takahashi: "Involvement of splenocytes' in the control of corpus luteum function in the rat." Endocrinologia Japonica. 35. 891-898 (1988)

Saito，S.，S.Matsuyama，K.Shiota 和 M.Takahashi：“脾细胞参与控制大鼠黄体功能”。

Kasuga, F., K. Shiota, M. Takahashi: "Significance of germ cells for the expression of testicular endocrine function in rats." J. Reprod. Fert., 87, 179-186, 1989.

Kasuga, F., K. Shiota, M. Takahashi：“生殖细胞对于大鼠睾丸内分泌功能表达的意义。”

Kadota,C.,M.Ohta,M.Takahashi: "Effects of androgen on progesterone secretion from,granulosa cells obtained from antral tollicles of rats" Endocrinologia Japonica. 37. (1990)

Kadota,C.,M.Ohta,M.Takahashi：“雄激素对从大鼠胃窦获得的颗粒细胞分泌黄体酮的影响”Endocrinologia Japonica。